A Phase II Study Using Rituximab Plus Venetoclax in the Front Line Treatment of Marginal Zone Lymphoma

Marginal Zone Lymphoma Clinical Trial

Official title:

A Phase II Study Using Rituximab Plus Venetoclax in the Front Line Treatment of Marginal Zone Lymphoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04416451
• Other study ID #: 20-115
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 4, 2021
• Est. completion date: June 2024

Study information

• Verified date: June 2023
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will help researchers understand how effective the combination of venetoclax and rituximab is in treating MZL in people who have not received a previous treatment for their cancer.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 6
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age greater than or equal to 18 years

• Histologically confirmed Marginal Zone Lymphoma

• Patients must have measurable disease as defined by at least one lymph node =1.5 cm or spleen >13 cm.

°Patients with intestinal MALT lymphoma must have disease that is detectable by EGD or colonoscopy with biopsy

• Patients with gastric MALT lymphoma must be h. pylori negative

°Patients who are h. pylori positive are allowed if they have failed a trial of h.pylori eradication

• Patients with gastric MALT lymphoma who are h. pylori negative or who have relapsed/refractory disease after h. pylori eradication must be ineligible for, have refused or failed gastric radiation therapy

• ECOG performance status = 1

• Life expectancy of greater than 2 years

• Patients must have normal organ function as defined below:

• Platelet count = 50,000 cells/mm^3

• Hemoglobin = 8.0 g/dL

• Absolute neutrophil count = 1000 cells/mcL. If there is documented bone marrow involvement, ANC must be >/= 500 cells/mcL

• Total bilirubin < 1.5 x upper normal institutional limits. In patients with Gilbert's disease or documented liver involvement, total bilirubin up to 3x ULN will be allowed

• AST(SGOT)/ALT(SGPT) <3 x institutional upper limit of normal unless elevation is caused by liver involvement with MZL

• AST(SGOT)/ALT(SGPT) <3 x institutional upper limit of normal unless elevation is caused by liver involvement with MZL

°OR Creatinine clearance >60 mL/min for patients with creatinine levels above institutional normal (by Cockcroft-Gault estimate or 12-24h creatinine clearance measurements).

• Ability to understand and the willingness to sign a written informed consent document.

• Able to swallow pills

• HIV-positive patients on combination antiretroviral therapy are eligible if their HIV is under adequate control with an antiretroviral regimen that has been stable for > 4 weeks, as long as the CD4 count is > 300. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

• Patients with Hepatitis B surface antibody serum positivity due to prior immunization, as well as those with Hepatitis B core antibody positivity with negative PCR on antiviral therapy will be eligible.

Exclusion Criteria:

• Patients who have had prior systemic therapy, including rituximab

• Patients who have had prior radiation therapy, with the following exception:

°Palliative radiotherapy RT is allowed but must be completed at least 1 week prior to treatment on this study, and prior baseline imaging studies or biopsies. Patients must meet criteria for measurable/assessable disease as outlined above after completion of RT

• Prior treatment with ibrutinib or other BTK inhibitor

• Patients with h. pylori-associated gastric MALT or stage I/II MZL will be excluded unless they are deemed to be unfit for radiation therapy with curative intent.

• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

°Patients with Hep B core ab positivity are allowed provided Hep B PCR is undetectable

• Lactating or pregnant women

• Participants unwilling to adhere to institutional guidelines for highly effective contraception for 12 months after the last dose of rituximab

• Patients who received moderate or strong CYP3A inhibitors (such as fluconazole, ketoconazole, and clarithromycin) within 7 days prior to the first dose of venetoclax.

• Patients who received moderate or strong CYP3A inducers (such as rifampin, carbamazepine, phenytoin, St. John's Wort) within 7 days prior to the first dose of venetoclax.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Marginal Zone Lymphoma

Intervention

Drug:
• Rituximab
Induction:Rituximab will be administered per institutional guidelines once per week for 4 weeks at a dose of 375 mg/m^2. Maintenance: In addition, patients will receive rituximab 375 mg/m2 starting on day 1 of the maintenance phase and repeated once every 3 months for 12 months (for a total of 4 infusions). On days when venetoclax and rituximab will both be administered, patients will take venetoclax prior to administration of rituximab.
• Venetoclax
Induction: Starting one week after the last induction dose of rituximab (approximately week 5), venetoclax will be administered orally at a flat dose of 100 mg daily and escalating each week to a target dose of 800 mg daily on the following schedule: Week 1: 100 mg Week 2: 200 mg Week 3: 400 mg Week 4: 800 mg Maintenance: Following the 4-week induction phase ramp-up of venetoclax, patients will begin their target dose of 800 mg venetoclax daily and continue this dose during the 24- month maintenance treatment phase. On days when venetoclax and rituximab will both be administered, patients will take venetoclax prior to administration of rituximab.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (All Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Commack (All Protocol Activities)	Commack	New York
United States	City of Hope Cancer Center (Data collection only)	Duarte	California
United States	Memorial Sloan Kettering Westchester (All Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (All protocol activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (All protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	New York	New York
United States	Memorial Sloan Kettering Rockville Centre (All Protocol Activities)	Rockville Centre	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	complete response rate (CRR)	Will be evaluated in this study using the RECIL criteria.	2 years
Secondary	overall response rates (ORR)	Overall response rate (ORR) will be measured as the number of patients that achieve a PR or CR per RECIL criteria.	2 years

External Links

•   Memorial Sloan Kettering Cancer Center